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Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord. J Pharmacol Exp Ther 2005 Sep;314(3):1101-8

Date

05/20/2005

Pubmed ID

15901793

DOI

10.1124/jpet.105.087130

Scopus ID

2-s2.0-23944521611   24 Citations

Abstract

We have previously shown that the naturally occurring levo-morphine at a subanalgesic picomolar dose pretreated i.t. induces antianalgesia against levo-morphine-produced antinociception. We now report that the synthetic stereo-enantiomer dextro-morphine, even at an extremely low femtomolar dose, induces antianalgesia against levo-morphine-produced antinociception using the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with dextro-morphine (33 fmol) time-dependently attenuated the i.t. levo-morphine-produced TF inhibition for 4 h and returned to the preinjection control level at 24 h. Intrathecal pretreatment with dextro-morphine (0.3-33 fmol), which injected alone did not affect the baseline TF latency, dose-dependently attenuated the TF inhibition produced by i.t.-administered levo-morphine (3.0 nmol). The ED(50) value for dextro-morphine to induce antianalgesia was estimated to be 1.07 fmol, which is 71,000-fold more potent than the ED(50) value of levo-morphine, indicating the high stereoselective action of dextro-morphine over levo-morphine for the induction of antianalgesia. Like levo-morphine, the dextro-morphine-induced antianalgesia against levo-morphine-produced TF inhibition was dose-dependently blocked by the nonopioid dextro-naloxone and its stereo-enantiomer levo-naloxone, a nonselective mu-opioid receptor antagonist. The antianalgesia induced by levo-morphine and dextro-morphine is reversed by the pretreatment with the glial inhibitor propentofylline (3.3-65 nmol), indicating that the antianalgesia is mediated by glial stimulation. The findings strongly indicate that the antianalgesia induced by levo-morphine and dextro-morphine is mediated by the stimulation of a novel nonopioid receptor on glial cells.

Author List

Wu HE, Thompson J, Sun HS, Terashvili M, Tseng LF

Author

Jonathan R. Thompson MD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analgesia
Animals
Dose-Response Relationship, Drug
Injections, Spinal
Male
Mice
Morphine
Naloxone
Neuroglia
Spinal Cord
Stereoisomerism
Xanthines
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